Obesity is a health problem of grave concern in western nations and the search for effective treatments has yet to come to fruition. The control of food intake and body weight involves peripheral (hormonal) and central (neural) mechanisms. One peripheral hormone that satisfies the criteria for being a signal of body fat is the pancreatic hormone, insulin. Insulin is released in proportion to fat mass, and when administered into the brain, reduces food intake and body weight. In the brain, the hypothalamic melanocortin family of peptides is thought to play an important role in the control of food intake. Administration of MC antagonists produce robust increases in food intake, while agonists lead to decreased intake. The present experiments are proposed to investigate the role of hypothalamic MC in the mediation of insulin's effects. The first series of studies will incorporate double-labeling in-situ hybridization techniques to assess whether neurons which produce MC peptides also contain receptors for insulin. The second series will assess whether there is a functional relationship between hypothalamic insulin receptors and MC neurons. This will be accomplished with in-situ hybridization and c-fos immunocytochemistry techniques. It is hypothesized that central administration of insulin will lead to changes in activation of MC neurons. Finally, the third set of studies will assess whether MC neurons mediate the effects of insulin on food intake. It is hypothesized that MC antagonists will block the hypophagic effects of central insulin administration